Summary Venous thromboembolism (VTE) has been called the single leading cause of preventable harm in hospitalized patients by AHRQ. Numerous studies have focused on improving prescription of VTE prophylaxis medication for hospitalized patients; however, prescription does not ensure administration. We found that VTE prophylaxis medication nonadherence among hospitalize patients is highly prevalent; on some floors patients miss only 5% of doses and on others nearly 40%. The most frequently documented reason for non- administration is patient refusal. Among patients with preventable VTE (defined as VTE in patients not receiving prophylaxis), the majority (72%) were prescribed optimal prophylaxis but missed one or more doses. Classically, interventions targeting medication nonadherence have been focused exclusively on outpatient settings, limiting their generalizability to hospitalized patients. In 2013, we were funded by the Patient Centered Outcomes Research Institute (PCORI) to develop and deliver a patient-centered, evidence-based intervention bundle in real-time using transactional electronic health record data to improve adherence to prescribed VTE prophylaxis for hospitalized patients. The goal of this intervention was to empower patients to make informed decisions about their VTE preventive care and improve VTE prophylaxis medication adherence in hospitalized patients in heterogeneous environments. Our research study showed significant improvement, with a 40% decline of nonadministration of pharmacologic VTE prophylaxis doses, and a 50% reduction in patient refusal. We further tested this intervention in a real-world setting where charge nurses on 8 different floors were given the patient education bundle to deliver; nonadherence decreased 47% and patient refusal decreased by 57%. We will scale up our intervention across diverse hospital settings, including a major academic medical centers and two community hospitals. Between these hospitals, VTE medication nonadherence ranges from 8.8% to 17.8%. We will deliver interactive, online, scenario-based education to frontline nurses regarding the importance of VTE prevention for hospitalized patients and will engage hospitalized patients who are at highest risk of VTE prophylaxis medication nonadherence using a patient-centered education intervention bundle. Our primary outcome is the proportion of administered VTE prophylaxis medication doses. Our secondary outcomes include the incidence of patient refusal for VTE prophylaxis medication, incidence of hospital- associated VTE using the validated AHRQ Patient Safety Indicator-12, and the proportion of patients with VTE who miss doses of prescribed prophylaxis. Successful completion of the proposed research will empower patients to make informed decisions about their VTE preventive care, increase VTE prophylaxis medication adherence, and improve delivery of patient- centered, defect-free VTE prevention to hospitalized patients across heterogeneous clinical settings.